We propose to examine the effect of various environmental factors (chemical and physicochemical) on the physiology, metabolism, virulence, and chemical composition of Neisseria gonorrhoeae. Initial studies will investigate whether changes occur in the chemical composition of N. gonorrhoeae during in vitro and in vivo cultivation. These properties will include: (1) the presence or absence of a capsule; (2) increased or decreased susceptibility to the bactericidal activity of normal human serum; (3) alterations in the permeability of the outer membrane; (4) qualitative or quantitative changes in the protein components of outer membrane; and (5) alteration in the amount or type of lipopolysaccharide produced. The chemical composition of cells grown on agar plates or by batch culture methods may not resemble the composition of cells grown in vivo. The effects of environmental factors may be best studied by continuous culture methods. With these procedures, we propose to examine the effects of growth rate, medium composition, nutrient limitation, and temerature on the colony type stability and chemical composition of N. gonorrhoeae. Additional studies will examine the effects of these variables on the metabolism of the gonococcus. The absence of significant endogenous metabolism would be a contributing factor in the rapid decrease in viability observed during transport of clinical specimens and for the autolytic nature of the gonococcus. We will investigate the nature and extent of endogenous metabolism of the gonococcus and whether it is influenced by environmental factors.